Chemotherapy-induced Thrombocytopenia (CIT)
Conditions
Brief summary
A Phase I Clinical Study to Evaluate the Safety, Tolerability, Immunogenicity, Preliminary Efficacy and Pharmacokinetics of SCB-219M in the patients with chemotherapy-induced thrombocytopenia (CIT)
Detailed description
The purpose of this trial is to evaluate the safety, tolerability, immunogenicity, and PK characteristics of single and multiple subcutaneous injections of SCB-219M for CIT, explore the MTD and BED, and preliminarily observe and evaluate efficacy. The trial is divided into a dose escalation phase (Ia) and an expansion phase (Ib).
Interventions
BIOLOGICALRecombinant Human Tumor Necrosis Factor Receptor II -Fc-TPO Mimetic Peptide Fusion Protein
Recombinant Human Tumor Necrosis Factor Receptor II -Fc-TPO Mimetic Peptide Fusion Protein for injection (Strength: 1 mg/ml, 0.5ml/vial)
Sponsors
Sichuan Clover Biopharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age: 18-75 years (inclusive), voluntary participation with signed informed consent and commitment to protocol-defined visits. 2. Body Weight: ≥40 kg. 3. Diagnosis: Histopathologically/cytopathologically confirmed malignant solid tumors or lymphoma. 4. Phase Ia: Platelet (PLT) & Treatment Status: <!-- --> 1. PLT \<75×10⁹/L during prior chemotherapy cycle; 2. Receiving mono/combination chemotherapy (may include targeted/immunotherapy). 5.Phase Ib: Stratified Requirements: * Group A (1st-line CIT prophylaxis/therapy): <!-- --> 1. PLT \<50×10⁹/L, or 2. PLT 50-75×10⁹/L. • Group B (2nd-line CIT therapy/refractory cases): Second-line CIT treatment for refractory or treated CIT patients who failed first-line therapy (rhTPO/IL-11) with platelet count \<50×10⁹/L 6.Refractory/Treated CIT Definition: * Platelet count remains \<50×10⁹/L or increases by \<20×10⁹/L within 14 days after completing first-line CIT therapy (e.g., rhTPO or rhIL-11), with baseline PLT \<50×10⁹/L at enrollment. 7.Toxicity Resolution: Prior anti-tumor toxicity ≤ Grade 2 (CTCAE v5.0) at enrollment (alopecia/vitiligo/subjective symptoms excluded). 8.ECOG PS: 0-2. 9.Life Expectancy: ≥3 months (investigator-assessed). 10.Baseline Laboratory (Pre-dose): * a) Creatinine ≤1.5×ULN; CrCl \>40 mL/min; * b) PT/APTT/INR 80-120% of normal range; * c) ANC ≥1.5×10⁹/L; * d) Hemoglobin ≥70 g/L; * e) Albumin ≥25 g/L. 11.Liver Function: * a) ALT/AST ≤3×ULN (≤5×ULN if liver metastasis); * b) Total bilirubin ≤2.0×ULN (Gilbert's syndrome/asymptomatic cholelithiasis exempted). 12.Contraception: * Fertile subjects must use ≥1 method: o Absolute abstinence; * Double-barrier (condom + spermicidal diaphragm); * IUD/hormonal contraceptives (oral/implant/patch/injection); * Hysterectomy/bilateral salpingectomy/tubal ligation (females or partners); * Vasectomy/azoospermia (males or partners). * Females: Negative serum β-HCG within 28 days; * Males: No sperm donation from first dose to 180 days post-last dose.
Exclusion criteria
1. Pregnancy/Lactation: Pregnant or breastfeeding females. 2. Hypersensitivity: Known allergy to protein-based drugs (e.g., recombinant proteins, mAbs) or excipients of the investigational product. 3. Active Infection: Acute infection requiring IV antibiotics without clinical control. 4. Prior Thrombopoietic Agents: • Group A: Use within specified windows pre-SCB-219M: o Trilaciclib: ≤3 weeks o Romiplostim: ≤2 weeks o TPO-RAs (e.g., eltrombopag), rhTPO, IL-11, or platelet transfusion: ≤10 days • Group B: Use within: o Romiplostim/rhTPO/IL-11: ≤7 days o TPO-RAs/platelet transfusion: ≤3 days 5. Anticoagulant Use: Anticoagulants/antiplatelet drugs ≤5 half-lives pre-dose or needed during study (aspirin washout ≥7 days). 6. Non-Chemotherapy Thrombocytopenia (within 6 months/unresolved): 1\) Clinically significant non-chemotherapy-induced thrombocytopenia (e.g., EDTA-dependent pseudothrombocytopenia) 2) Hematologic malignancies (excluding lymphoma; e.g., leukemia) 3) Multiple myeloma 7.Bleeding Events (within 2 weeks pre-screening): • Group A: ≥Grade 2 (WHO Bleeding Scale) * Group B: ≥Grade 3 (WHO Bleeding Scale) 8.Non-CIT Thrombocytopenia Etiologies: 1) Primary immune thrombocytopenia (pITP) 2) Bone marrow failure (e.g., aplastic anemia, Fanconi anemia) 3) Myeloproliferative disorders/MDS 4) Hypersplenism secondary to hematologic/autoimmune diseases 9.Splenectomy/Splenic Effects: Splenic metastasis affecting hematopoiesis; splenectomy/splenic artery embolization ≤12 weeks pre-enrollment. 10.Uncontrolled Cardiovascular Disease: * NYHA Class III/IV heart failure * Pro-thrombotic conditions (e.g., atrial fibrillation, unstable angina) * QTc \>470 ms (\>480 ms with bundle branch block) * Myocardial infarction ≤6 months (Note: Pacemaker/ICD users with normal function eligible) 11.Thrombotic/Coagulation Disorders: * Coagulopathies * Arterial/venous thrombosis ≤3 months (excluding PICC-related thrombosis) * Transient ischemic attack ≤3 months 12.Major Procedures/Radiotherapy: Major surgery/radiotherapy ≤4 weeks pre-dose (except toxicity ≤Grade 2 \[CTCAE v5.0\], alopecia/vitiligo permitted). 13.CNS Metastases: Active/untreated CNS or leptomeningeal metastases (asymptomatic brain metastases allowed). 14.Uncontrolled Hypertension: Resting SBP ≥160 mmHg and/or DBP ≥100 mmHg (two measurements, 2h apart). 15.Active Infections: * HIV seropositivity * Active HBV (HBsAg+ andHBV DNA \>LLOQ) * Active HCV (anti-HCV+ andHCV RNA \>LLOQ) 16.Live Vaccines: Live attenuated vaccines ≤4 weeks pre-dose (COVID-19 vaccines permitted except Ad5-vectored type \[requires investigator assessment\]). 17.Concurrent Clinical Trials: Participation in other drug/device trials ≤4 weeks pre-dose or planned during study. 18.Investigator's Discretion: Poor compliance or other factors deemed unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose escalation: Occurrence of DLT. | Occurrence of DLT from enrollment to day 21. | Occurrence of DLT |
| Dose escalation: Frequency of DLT. | Frequency of DLT from enrollment to day 21. | Frequency of DLT |
| Dose escalation and Dose expansion:Occurrence of AE. | 28 days after the last administration of SCB-219M | number, frequency,and charaterization of AEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose escalation: AUC0-24h | up to 21 days after treatment | AUC0-24h: Area under the serum concentration-time curve from 0 h to 24 h |
| Dose escalation: AUC0-last | up to 21 days after treatment | AUC0-last :Area under the serum concentration-time curve from 0 h on Day 1 to the last time point with a quantifiable concentration |
| Dose escalation: AUC0-inf | up to 21 days after treatment | AUC0-inf : Area under the serum concentration-time curve from 0 h extrapolated to infinity |
| Dose escalation: t1/2 | up to 21 days after treatment | t1/2 : Apparent half-life |
| Dose escalation: CL/F | up to 21 days after treatment | CL/F: Systemic clearance |
| Dose escalation: Vz/F | up to 21 days after treatment | Vz/F: Volume of distribution |
| Dose escalation: Cmax | up to 21 days after treatment | Cmax : Maximum serum concentration |
| Dose escalation: Preliminary efficacy assessment.The percentage of subjects requiring platelet infusion and the frequency of infusion during the DLT observation period. | up to 28 days after administration | The percentage of subjects requiring platelet infusion and the frequency of infusion during the DLT observation period. |
| Dose escalation: Preliminary efficacy assessment. | up to 28 days after administration | Duration of PLT count ≥50×10\^9/L and percentage of subjects during the DLT observation period. |
| Dose expansion:：PK parameters of SCB-219M were established after repeated abdominal subcutaneous injections. | up to 168 hours after the last treatment | The PK parameters include: C₀, Cmax/D, Css\_min, Cmax\_ss, Cav\_ss, Rac, tmax, AUC₀-last, AUC₀-inf, AUCss, DF, MRT, t₁/₂, etc. |
| Dose expansion: Preliminary efficacy assessment. | 28 days after the last administration of SCB-219M | Incidence of grade 2/3/4 thrombocytopenia (CTCAE version 5.0). |
| Dose expansion: ：Platelet response onset time (days), duration of platelet effect maintenance (days), and overall response rate (%). | 28 days after the last administration of SCB-219M | Key efficacy endpoints per protocol: 1. Time (days) to first achievement of platelet counts ≥50×10⁹/L, ≥75×10⁹/L, and ≥100×10⁹/L post-dose ;; 2. Duration (days) of sustained platelet count maintenance at or above prespecified thresholds (≥50×10⁹/L, ≥75×10⁹/L, ≥100×10⁹/L); 3. Responder rate (%) , defined as the proportion of subjects achieving predefined platelet count thresholds. |
| Dose escalation: λz | up to 21 days after treatment | λz: Elimination rate constant |
| Dose escalation: Cmax/D | up to 21 days after treatment | Cmax/D :Dose normalized Cmax |
| Dose escalation: tmax | up to 21 days after treatment | tmax : Time to Cmax |
Countries
China
Outcome results
None listed